Apparatus and method for delivering controlled quantities of one or more agents to the eye

ABSTRACT

A flat strip of supporting material, such as filter paper, having marked reference locations on each of one or more legs, for delivering controlled quantities of one or more agents to the adnexa of the eye simultaneously upon dispensing a liquid to the strip at the appropriate reference location.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. application Ser. No.10/158,471 filed May 30, 2002, now U.S. Pat. No. 7,018,646.

FIELD OF INVENTION

This invention relates to an apparatus and method for applyingcontrolled quantities of curative, diagnostic or therapeutic agents tothe eye. This invention relates particularly to a flexible strip ofsupporting material incorporating one or more agents, which is wettedand touched to the surface structures of the eye.

BACKGROUND

Diagnostic, curative or therapeutic agents are administered to the eyein small quantities during ophthalmic examinations and treatments. It isoften convenient to administer more than one agent at a time, such as adye and an anesthetic, so that the eye is prepared simultaneously formultiple tests. Eye droppers and solid applicators are commonly used toadminister these agents, but each has its own disadvantages.

Eye droppers are squeeze bottles that exude one drop of solution at atime, and provide multiple doses of a given agent in a single bottle.Although they are convenient, the pharmacological solutions used in theeyedroppers have disadvantages. The solutions are unstable over time andtherefore have a limited shelf life. Temperature fluctuations can causeprecipitation of various compounds, so less ophthalmic agent isadministered to a patient than would be expected in a full solution, oran irritating solid aggregate may be dispensed into a patient's eye.Precipitation can also occur if an eye dropper bottle is not closedtightly thereby causing evaporative loss of water. After the bottles ofsolution are opened, the solutions may be contaminated by microbes. Overtime, this microbial contamination grows and degrades the agents insolution, reducing their benefit for patients and adding the risk ofinfection. To deal with this problem and to increase the shelf life to acommercially-viable period of time, various preservatives are added toophthalmic solutions to prevent microbial growth. Unfortunately, manypatients are allergic to these preservatives, and the preservatives aretherefore irritating to the patient's eye. Single-use vials of solutionare available preservative-free, but these vials are inconvenient to useand expensive. It is desirable to provide a cost-effective, convenientdispenser of controlled quantities of ophthalmic agents that remainssterile until use, and has no preservatives.

Eyedroppers have other disadvantages. The volume of fluid dispensed byan eyedropper is often more than an eye can hold, and therefore theexcess fluid leaks out. When it does, it is impossible to determine theamount of medicament administered to the eye. In addition, the liquidthat leaks out of the eye can stain a patient's clothing, such as thecase when fluorescein sodium, a dye commonly used in ophthalmicdiagnoses, is used. Also, an eye dropper is not satisfactory when verysmall quantities of medications are needed, for example the quantitiesless than that present in one drop of a standard ophthalmic eyedropperformulation. It is desirable to administer ophthalmic agents in a waythat delivers a known small quantity that remains in the patient's eye.

The prior art is replete with single-use applicators made of filterpaper, plastic rods, polymer film or other dry substrate materials thatare physically touched to the eye or adnexa. A solution of the agent ofchoice, such as fluourescein sodium, is applied to the substrate andallowed to dry. The dry, impregnated applicators are applied directly tothe patient's eye, and the pharmacological agent dissolves in thepatient's tears. These devices suffer serious disadvantages. First,application of a dry surface to the eye is very irritating. Second,dissolution into the tears of the eye is slow because of the extremelysmall volume of fluid present initially. The problem is exacerbated ifthe patient is suffering from dry eye syndrome, a common presentingcomplaint in ophthalmology. Plus, waiting for dissolution of theophthalmic agent is a lengthy process, prolonging the irritation anddiscomfort for the patient. It is desirable to provide a method thatdelivers the agents quickly and with an applicator that is minimallyirritating to the eye.

It is common practice to administer diagnostic dyes with small strips offilter paper that have been soaked in the dye and dried. Tosimultaneously deliver more than one agent at a time, a practitioner mayadd a drop of anesthetic to one end of the strip, dissolving the dye,and then touch the adnexa of the eye with the wetted filter paper. This,too, however, has its disadvantages. The filter paper is insufficientlyrigid to hold the drop, and the excess fluid drops off the end of thestrip. As a result, less anesthetic is given to the patient than what isin one drop, but the actual quantity is unknown, and additionalanesthetic often must be administered by eyedroppers. Furthermore, uponwetting, many of the strips droop, complicating their handling. Oftenthe dye strips are manufactured with much more dye than what is reallyneeded for the diagnostic procedure, leading to waste, extra expense andpossible damage to the patient's clothing. Practitioners in such caseswipe off the excess dye, which further illustrates the sub-optimal stateof the art. Again, it is desirable to administer ophthalmic agents in away that delivers a known quantity that remains in the patient's eye.

Additional problems arise when delivering multiple agents to the eyesimultaneously. For example, it is common practice to administer a dyeand an anesthetic combination during the procedure of measuringintraocular pressure using applanation or other forms of tonometry. Whencombined in a solution for application by eyedropper, however, many dyesand anesthetics, such as fluorescein sodium and proparacaine, formprecipitates and fall out of solution or otherwise adversely affect thesolubility of the companion agents. Interestingly, the same is true forthe preparation of ophthalmic strips: many common ophthalmic agents formprecipitates as they dry on the strip or otherwise adversely affect thesolubility of the other agents, thereby rendering them useless. Thismeans that heretofore eyedroppers and strip applicators have not beenoptimal delivery devices for delivering multiple agents to the eye.

Therefore, it is an object of this invention to provide an apparatusthat simultaneously delivers a known quantity of one or more ophthalmicagents to the eye in a single application, with little or no waste. Itis another object of this invention to provide an apparatus thatdelivers multiple ophthalmic agents in a disposable, sterile, single-useapplicator for immediate use. It is a further object to provide anapplicator having extended shelf-life with no preservatives. It is afurther object of this invention to deliver ophthalmic agents in aminimally irritating way.

SUMMARY OF THE INVENTION

The present invention is a strip of supporting material forsimultaneously delivering controlled quantities of one or moreophthalmic agents to the eye. The strip has one or more legs into whichcontrolled amounts of agents are incorporated. Typically only one agentis incorporated per leg, however more than one agent may be incorporatedper leg if the agents are compatible with one another and do notadversely affect the solubility of the others when combined on thestrip. Each leg is marked with a reference location to show where a dropof liquid should be placed to deliver a controlled amount of agent tothe eye. The reference mark is a thin line or dot of ink that does notspread or dissolve when wetted, or a notch. To use the strip, a drop ofliquid, generally sterile saline or contact lens solution, is applied toone or more legs at the reference mark. The moistened strip is thenapplied briefly to the underside of the upper or lower eyelid, whichcauses transfer of the agents to the surface structures of the eye.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top-view schematic illustration of a one-legged stripshowing multiple reference marks.

FIG. 2 is a cross-section view of the device in FIG. 1.

FIG. 3 is a top-view schematic illustration of a two-legged strip withlines as reference marks.

FIG. 4 is a top-view schematic illustration of a two-legged strip withdots as reference marks.

FIG. 5 is a top-view schematic illustration of a two-legged strip withnotches as reference marks.

FIG. 6 is a top-view schematic illustration of a double-ended,two-legged strip with lines as reference marks.

FIG. 7 is a top-view schematic illustration of a double-ended,four-legged strip with lines as reference marks.

FIG. 8 is a top view of a sandwich strip with lines as reference marks.

FIG. 9 is a cross-section view of the device in FIG. 8.

FIG. 10 is a top-view schematic illustration of a three-legged stripshowing multiple reference marks.

DETAILED DESCRIPTION OF THE INVENTION

FIGS. 1 to 10 illustrate several embodiments of the present invention.In all embodiments, the supporting material is a strip of material thatis flexible yet rigid enough to support a drop of liquid. Preferablyeach strip, referenced throughout generally as 10, is made of filterpaper, typically methylcellulose, but may also be made of other types ofpaper, fabric, membrane, polymer, or other material that is physicallystrong enough to support the liquid and chemically compatible with theeye and ophthalmic agents. The supporting material is preferablysubstantially non-water soluble, but may be water soluble, substantiallywater soluble, or non-water soluble, depending on, among other factors,the agents used and method of manufacture. To increase convenience anddecrease cost, both ends of the strip may have one or more legs 11 withincorporated agents. An alternative embodiment shown in FIGS. 8 and 9provides a device with two legs 11 of supporting material 10 separatedby a barrier 18 substantially impermeable to the liquid and ophthalmicagents, referred to herein as a sandwich device. The barrier may bepositioned between the legs to form an integrated component, where oneleg is attached to one side of the barrier and the other leg is attachedto the other side of the barrier. Alternatively, the barrier coating maybe attached to each leg on its underside, and the legs attached to thehandle, with the barrier side of each leg facing one another.

The device is generally up to 1.5 cm in total width, indicated in FIG. 1as w1, FIG. 3 as w2, FIG. 8 as w3 and FIG. 10 as w4. For illustrationclarity, total width is indicated only on FIGS. 1, 3, 8 and 10. Thedevice may have more than one leg 11, and the total width of the stripdepends, in part, on the number of legs. Preferably each leg is about0.5 cm wide, such that the device is 0.5 cm wide for one leg, asillustrated in FIGS. 1, 6 and 8; 1.0 cm wide for two legs attachedside-by-side, such as that of FIGS. 3, 4, 5 and 7; and 1.5 cm wide forthree or more legs attached side-by-side on each end, such as that ofFIG. 10. The device is generally about 6 cm long for single-ended use,as indicated in FIG. 1 as t1. The device is generally about 9 cm longfor double-ended use, as indicated in FIG. 6 as t2, to make the deviceeasier to handle. For illustration clarity, length is indicated only onFIGS. 1 and 6. The single-sided device is generally about 0.03 cm thick,as illustrated in FIG. 2 as t1. The sandwich device is generally about0.07 cm thick, as illustrated in FIG. 9 as t2.

Each strip is marked with one or more visible reference marks indicatingwhere to place a drop of liquid on each leg to deliver a controlledamount of one or more agents to the eye. The marks should be made with asubstance that does not spread or dissolve when wetted. The location ofthe marks will depend on the desired dosage to be delivered, theconcentration of the agent incorporated into the strip, and the volumeof the liquid to be applied. FIG. 1 shows a graduated strip with lines20, each marking a separate location for a drop of liquid to be appliedto deliver a different dose. FIGS. 3, 6, 7, 8 and 10 show lines 20 usedas reference marks for delivering single doses. Alternative types ofreference marks can also be used. FIG. 4 shows dots 21 as the referencemark and FIG. 5 shows notched cut-outs 22.

A drop of liquid is applied to the filter paper at the desired location.The drop is substantially absorbed by the strip and preferably deliveredby an eye dropper. The farther the liquid is placed from the end of thestrip that touches the eye, the more agent is delivered to the eye. Forexample, if a drop of fluid is applied 0.5 centimeter from the endinstead of 1.0 centimeter, half as much of the agent is delivered to theeye. For the device shown in FIGS. 8 and 9, a drop is applied to oneleg, allowed to absorb, and then another drop is applied to the otherleg on the other side of the strip. The liquid can be any solution thatis compatible with the eye and with the agents, such as saline,distilled water, or contact solution. Preferably sterile saline is used.The liquid spreads through the paper by capillary action dissolving theincorporated compounds and bringing them toward the end of the strip.From the end of the strip, the solution of compounds is delivered bybriefly touching the end of the strip to the adnexa of the eye, whichrapidly draws off fluid from the end of the strip. The wetted strip istouched for a very short period, preferably no more than a second.

The strips are prepared by methods known in the art. In general, asolution having an agent of desired concentration is applied to sheetsor strips of filter paper. The agent may be absorbed into or adsorbedonto the substrate, and all molecular methods of adhering the agent tothe substrate are referred to herein as incorporating the agents. Thesubstrate is preferably substantially non-water soluble, but may bewater soluble, substantially water soluble, or non-water soluble,depending on, among other factors, the agents used and method ofmanufacture. The filter paper is dried and then cut into segments ofspecific size to deliver a known quantity of agent. The segments areintegral with or otherwise attached to an applicator handle 14. Thehandle segment can be made of any suitable material that preventsmoisture from being drawn from the hand holding the strip, such asvarnished paper. The devices are then sealed in sterile packaging thatis preferably substantially impervious to light that can deactivate theagents.

The agents can be any drug or chemical used to treat, cure, prevent, ordiagnose ophthalmic problems, such as local anesthetics, diagnosticdyes, pupillary dilators, antibiotics, antivirals, antiglaucomatouspreparations, nonsteroidal antiinflammatories, viral and bacterialdiagnostic agents. Local anesthetics include proparacaine, andtetracaine. Diagnostic dyes include fluorescein sodium, methylene blueand rose Bengal. Typically only one agent is incorporated per leg.However, more than one agent may be incorporated per leg if the agentsare compatible with one another and do not adversely affect thesolubility of the others when combined on the strip.

In one example, the strips are prepared by soaking sheets or strips offilter paper first in a solution of 50 mg/ml fluorescein and then in a45 mg/ml of proparacaine. The sheets are dried, resulting in 1.35 mg/cm²of fluorescein and 1.2 mg/cm² of proparacaine on the sheet,respectively. The sheets are then cut into segments and the referencemark is applied 1.5 cm from the applicator strip end. In anotherexample, the strips are prepared by soaking sheets or strips of filterpaper in 20 mg/ml solution of tetracaine hydrochloride, and dried,resulting in 0.540 mg/cm² tetracaine hydrochloride on the sheet. Thesheets are cut into segments and the reference mark is applied 1.5 cmfrom the applicator strip end. The strips are then attached to a handle,packaged, and sterilized.

While there has been illustrated and described what is at presentconsidered to be a preferred embodiment of the present invention, itwill be understood by those skilled in the art that various changes andmodifications may be made, and equivalents may be substituted forelements thereof without departing from the true scope of the invention.Therefore, it is intended that this invention not be limited to theparticular embodiment disclosed as the best mode contemplated forcarrying out the invention, but that the invention will include allembodiments falling within the scope of the appended claims.

1. An apparatus for delivering one or more agents to the eye comprising:a) a strip of substantially non-water soluble supporting material forapplication to the eye; b) one or more agents incorporated into thestrip; and c) one or more visible reference marks indicating where toplace a drop of liquid on the strip to dispense a controlled amount ofone or more agents to the eye.
 2. The apparatus of claim 1 wherein thestrip is attached to an applicator handle.
 3. The apparatus of claim 1wherein one or more agents is selected from the group of localanesthetics, diagnostic dyes, pupillary dilators, antibiotics,antivirals, antiglaucomatous preparations, nonsteroidalantiinflammatories, viral and bacterial diagnostic agents.
 4. Theapparatus of claim 1 wherein the agent is tetracaine hydrochloride. 5.An apparatus for delivering one or more agents to the eye comprising: a)a strip of substantially non-water soluble supporting material forapplication to the eye wherein at least one end of the strip is dividedinto at least two legs; and b) one or more agents incorporated into eachof the legs such that a controlled amount of each agent is delivered tothe eye upon application of liquid to each leg.
 6. The apparatus ofclaim 5 wherein the strip is attached to an applicator handle.
 7. Theapparatus of claim 5 wherein one or more agents is selected from thegroup of local anesthetics, diagnostic dyes, pupillary dilators,antibiotics, antivirals, antiglaucomatous preparations, nonsteroidalantiinflammatories, viral and bacterial diagnostic agents.
 8. Theapparatus of claim 5 further wherein a first leg incorporates dye and asecond leg incorporates anesthetic.
 9. The apparatus of claim 5 whereinthe legs are separated by a barrier substantially impermeable to theagents and the liquid.